A Study of LY2801653 in Advanced Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Drug: Cisplatin; Drug: Ramucirumab; Drug: LY2801653; Drug: Cetuximab; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01285037

13008

I3O-MC-JSBA (Other Identifier)

Details and patient eligibility

About

Part A- The purpose of this study is to determine a safe dose of LY2801653 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2801653 in this participant population. Efficacy measures will be used to assess the activity of LY2801653.

Part B- The dose determined in Part A will be used along with efficacy measures to assess the activity of LY2801653 in participants with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma (HNSCC), uveal melanoma with liver metastasis, and cholangiocarcinoma.

Part C - the objective of Part C is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with HNSCC when taken with standard doses of cetuximab Part D - the objective of Part D is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with a standard dose of cisplatin.

Part E - the objective of Part E is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with cholangiocarcinoma when taken with gemcitabine plus cisplatin.

Part F - the objective of Part F is to determine a recommended Phase 2 dose of LY2801653 that may be safely given to participants with gastric cancer when taken with ramucirumab.

Full description

Parts C and D were added to the registration in November, 2013, per protocol amendment. Parts E and F were added to the registration in February, 2015, per protocol amendment.

Enrollment: 190 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Part A- Diagnosed with advanced and/or metastatic cancer during dose escalation
• Part B- Diagnosed with adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver with metastasis, or cholangiocarcinoma
• Part C - Diagnosed with head and neck squamous cell carcinoma and have received at least one prior platinum-based systemic therapy
• Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
• Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
• Part F - Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma (participants with adenocarcinoma of the distal esophagus are eligible if the primary tumor involves the GEJ). Participants must be ramucirumab naïve. Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. human epidermal growth factor receptor 2 (HER2)/neu status should be documented, if known.
• Must be at least 18 years of age
• Adequate hematologic, renal, and liver functions
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Ability to swallow capsules, with the exception of head and neck squamous cell carcinoma participants who may have study drug crushed and administered through a feeding tube

Exclusion criteria

• Have serious preexisting medical conditions that would preclude participation in the study
• Have a chronic underlying infection
• Have symptomatic central nervous system (CNS) malignancy or metastasis
• Have current acute or chronic leukemia
• Are pregnant or lactating
• Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
• Have a history of congestive heart failure with a New York Heart Association class greater than 2, unstable angina, recent myocardial infarction (within 6 months of study enrollment), transient ischemic attacks, stroke, or arterial or venous vascular disease
• Have a QTc interval greater than 470 msec
• For participants in Part B, C, D, E, and F, a tumor tissue sample is mandatory, when safe and feasible, for biomarker analysis

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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190 participants in 1 patient group

LY2801653

Experimental group

Description:

This study consists of a dose escalation of LY2801653 (Part A) followed by dose confirmation cohorts in four tumor types (adenocarcinoma of the colon or rectum, head and neck squamous cell carcinoma, uveal melanoma with liver metastasis, and cholangiocarcinoma) (Part B). Part C consists of dose determination for LY2801653 in combination with cetuximab in participants with head and neck squamous cell carcinoma followed by an expansion cohort. Part D consists of dose determination for LY2801653 in combination with cisplatin in participants with cholangiocarcinoma followed by an expansion cohort. Part E consists of dose determination for LY2801653 in combination with gemcitabine and cisplatin. Part F consists of dose determination for LY2801653 in combination with ramicirumab.

Treatment:

Drug: Gemcitabine

Drug: Cisplatin

Drug: LY2801653

Drug: Ramucirumab

Drug: Cetuximab